Evidence map›Paper›PMID 23997176›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013

Functional expression of the TMEM16 family of calcium-activated chloride channels in airway smooth muscle.

George Gallos, Kenneth E Remy, Jennifer Danielsson, Hiromi Funayama, Xiao Wen Fu, Herng-Yu Sucie Chang, Peter Yim, Dingbang Xu, Charles W Emala

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 59 citations in OpenAlex.

  1. Benzbromarone as adjuvant therapy for cystic fibrosis lung disease: a pilot clinical trial.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2024
    Trial
  2. Review
  3. Article
  4. [Transmembrane protein 16A--a new target for the treatment of airway inflammatory diseases].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. The CaActa pharmaceutica Sinica. B · 2021
    Review
  14. Article
  15. Review
  16. Article
  17. Pharmacological Inhibition and Activation of the CaInternational journal of molecular sciences · 2020
    Article
  18. Review
  19. Agonism of the TMEM16A calcium-activated chloride channel modulates airway smooth muscle tone.American journal of physiology. Lung cellular and molecular physiology · 2020
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

George GallosDept. of Anesthesiology, 622 W. 168th St. P&S Box 46, Columbia Univ. College of Physicians and Surgeons, New York, NY 10032. gg2125@columbia.edu.
Kenneth E Remy
Jennifer Danielsson
Hiromi Funayama
Xiao Wen Fu
Herng-Yu Sucie Chang
Peter Yim
Dingbang Xu
Charles W Emala
Columbia University · USNational Institutes of Health Clinical Center · USTsurumi University · JP

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024156 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$53.0M
Neuromuscular blocker-induced asthma during anesthesiaR01GM065281 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI EMALA, CHARLES W · 2003 to 2018
$5.4M
THERAPEUTIC TARGETING OF THE GABAA CHANNEL ON AIRWAY SMOOTH MUSCLEK08GM093137 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GALLOS, GEORGE · 2010 to 2014
$628k
NCRR NIH HHS ULI RR 024156NIGMS NIH HHS GM008464NIGMS NIH HHS GM065281NIGMS NIH HHS GM093137NIGMS NIH HHS K08 GM093137NIGMS NIH HHS R01 GM065281
6 · The paper itself

Abstract

Airway smooth muscle hyperresponsiveness is a key component in the pathophysiology of asthma. Although calcium-activated chloride channel (CaCC) flux has been described in many cell types, including human airway smooth muscle (HASM), the true molecular identity of the channels responsible for this chloride conductance remains controversial. Recently, a new family of proteins thought to represent the true CaCCs was identified as the TMEM16 family. This led us to question whether members of this family are functionally expressed in native and cultured HASM. We further questioned whether expression of these channels contributes to the contractile function of HASM. We identified the mRNA expression of eight members of the TMEM16 family in HASM cells and show immunohistochemical evidence of TMEM16A in both cultured and native HASM. Functionally, we demonstrate that the classic chloride channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), inhibited halide flux in cultured HASM cells. Moreover, HASM cells displayed classical electrophysiological properties of CaCCs during whole cell electrophysiological recordings, which were blocked by using an antibody selective for TMEM16A. Furthermore, two distinct TMEM16A antagonists (tannic acid and benzbromarone) impaired a substance P-induced contraction in isolated guinea pig tracheal rings. These findings demonstrate that multiple members of this recently described family of CaCCs are expressed in HASM cells, they display classic electrophysiological properties of CaCCs, and they modulate contractile tone in airway smooth muscle. The TMEM16 family may provide a novel therapeutic target for limiting airway constriction in asthma.

Indexed as

AnimalsAnoctamin-1AnoctaminsAsthmaBenzbromaroneBronchiChloride ChannelsChronic DiseaseGuinea PigsHumansMembrane ProteinsMultigene FamilyMyocytes, Smooth MuscleNeoplasm ProteinsPatch-Clamp TechniquesPrimary Cell CultureANO1 protein, humanANO2 protein, humanAnoctamin-1AnoctaminsBenzbromaroneChloride ChannelsMembrane ProteinsNeoplasm ProteinsTanninsairway smooth muscleelectrophysiologyimmunohistochemistryMQAERT-PCR

Identifiers

PMID23997176
PMCPMC3840275
OpenAlexW2158893295

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.